Research Summary:
Our laboratory has investigated the structure and replication of telomeres using yeast Saccharomyces cerevisiae as a genetic model system. Telomeres are the structures present at the termini of eukaryotic chromosomes composed of G+T-rich DNA and a plethora of proteins that allow complete replication of the telomere and protection against factors that can act to degrade chromosomes. We have been exploring several novel aspects of telomere function. Multiple studies have implicated defects in telomeres and the onset of oncogenesis and chromosomal catastrophe. While most eukaryotic telomeres are replicated by the reverse transcriptase telomerase, we have focused on the second recombinational mode of telomere addition and deletion, both of which are highly maintained in vertebrates. Some protein complexes involved in this recombination pathway are present exclusively at the telomere while others are present both in replication and DNA repair. Using alleles of mutations in gene that encode components of these complexes, we have investigated the mechanism of telomere recombination. These studies have led to the discovery that telomeres have an epigenetic and heritable component. These latter finding provides a completely novel view of telomere regulation in yeast and in vertebrate oncogenesis.